Embryonic erythrocytes have the dual functions of iron storage and O2 transport and represent a fundamental difference between erythropoiesis in embryos and adults. High levels of ferritin (greater than 15 times adult levels) have been observed in the embryonic erythrocytes of humans, mice, chicks, and frogs. The inducibility of red cell ferritin synthesis by iron, the accessibility of embryonic erythrocyte iron stores to the embryo, and the ontogenetic coordination of transferrin saturation and concentration with erythrocyte iron storage indicate the importance of erythrocyte iron storage during ontogeny, which may be related to unique structural features of red cell ferritin. In order to understand the mechanism of the ontogenetic change in red cell ferritin content and the accessibility of red cell iron stores, experiments will be performed on the following topics: 1. Regulation of red cell ferritin synthesis - (a) ontogenetic changes in nuclear proteins during erythroid maturation, (b) the influence of transferrin saturation and structure on red cell iron storage, (c) translation of red cell ferritin mRNA, (d) iron storage in murine mutants. 2. Relation of red cell ferritin structure to availability of storage iron - (a) location of Ser, Gly in primary structure, (b) effect of protein modification on iron release, (c) nature of the iron-protein interface.